The purpose of this project is to understand better the development of the endometrium and oocyte in women and to investigate the role of gonadal steroids in these processes. The process of uterine remodeling that is so remarkable in the mammalian uterus is achieved through coordinated proliferation, differentiation and cell death. While the gonadal steroids estradiol and progesterone appear to be required for these organ-specific processes, the mechanism(s) by which these processes are regulated remain unclear. Potential mediators of estrogen action include IGF-1 and c-Myc, a transcription factor known to be induced by growth factors. We used a well-characterized in vivo ovariectomized mouse model to correlate sex steroid-induced proliferation with the induction of IGF-1 and c-Myc mRNA in the uterine endometrium. We have found that IGF-1 and c-Myc levels parallel each other and the estrogen-induced processes of differentiation in this model, suggesting that they are important to proliferation. The induction of IGF-1 by GH in other tissues prompted an evaluation of whether the GH receptor was present in the endometrium, based on the hypothesis that GH might act directly on the endometrium and so modulate estrogen effect. Previous findings that the GH receptor was present throughout the endometrium, also showed that GH was present in the myometrium. Further studies revealed that GH receptor was greater in leiomyomas than in surrounding myometrium, suggesting that GH reduction by octreotide might be a novel therapeutic approach to these lesions.